2199. Commercial Intravenous Immunoglobulin (IVIG) Preparations Contain Functional Neutralizing Antibodies Against the Staphylococcus aureus Cytotoxin LukAB
Session: Poster Abstract Session: Host-Pathogen Interactions
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • IDWeekPoster_10.21_JBW_Final[1].pdf (2.6 MB)
  • Background: The pathogenesis of Staphylococcus aureus is mediated by an array of virulence factors. The leukotoxin LukAB is critical for S. aureus pathogenesis in numerous models. Intravenous immunoglobulin (IVIg) is often used for S. aureus infections when there is concern for toxin production (e.g., toxic shock syndrome). The primary aim of this study was to assess the binding and neutralization potential of commercially available IVIg against LukAB. A secondary aim was to examine the lot-to-lot variability of IVIg in the binding and neutralization of LukAB

    Methods: We studied fifteen distinct lots of IVIg preparations. Antibodies targeting LukAB in IVIg samples were measured using enzyme-linked immunosorbent assay (ELISA), and quantified by comparison to a human monoclonal anti-LukAB IgG. Antibody function was assessed using a cytotoxicity assay. Function was measured as a ratio of neutralization units per ELISA units (NU:EU). The functional antibodies in IVIg were compared to serum samples of subjects with invasive S. aureus disease (both acute and convalescent) and healthy controls.

    Results: The relative variability between IVIg lots was 12.9%.  The mean concentration by ELISA of LukAB binding was 777.4 U/mL (SD ± 100).  Sera obtained from healthy controls contained a mean of 89 U/mL (SD+69.2), acutely infected subjects contained 186.9 U/mL (SD ± 287.2), and convalescent sera contained 456 U/mL (SD ± 484.64). The neutralizing capacity of the samples is displayed in Figure 1. There was no difference in mean NU:EU between groups. The variability of neutralization between IVIg lots was very low. 

    Conclusion:  Commercial preparations of human IVIg contain substantial levels of antibodies targeting the important S. aureus cytotoxin LukAB. Importantly, these antibodies are highly functional in the neutralization of this toxin, equivalent to those from patients recovering from invasive disease. We found remarkably little lot-to-lot variation in the amount or quality of LukAB antibodies. These findings raise interesting questions regarding the adaptive immune response to staphylococcal carriage and disease, and further characterization of functional antibodies will be important given the frequent clinical use of IVIg for severe S. aureus infections.

    James Wood Jr., MD1, Lauren Jones, BS2, Nicole Soper, MT2, C. Buddy Creech, MD, MPH, FPIDS3 and Isaac Thomsen, MD, MSCI2, (1)Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville,, TN, (2)Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, (3)Vanderbilt Vaccine Research Program and Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN

    Disclosures:

    J. Wood Jr., None

    L. Jones, None

    N. Soper, None

    C. B. Creech, None

    I. Thomsen, None

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